Purpose: prostaglandin (PG)I2 is a remarkable anti-carcinogenic agent mainly produced by vascular endothelial cells (EC). Since no studies have yet analyzed the biosynthetic pathway of PGI2in HNSCC, we studied this pathway in a large cohort of patients.
Experimental Design and results: We analysed samples of paired HNSCC and contralateral non-tumoral mucosa from 75 patients for mRNA levels of cyclooxygenase-isoenzymes, thromboxane A-synthase and PGI-synthase by real-time-PCR. As expected, cyclooxygenase-2 expression was increased in HNSCC samples. In contrast, levels of PGI-synthase mRNA were lower in the tumor samples. mRNA levels of cyclooxygenase-1 and thromboxane A-synthase were similar in mucosa and HNSCC samples. Consistently, expression of PGI-synthase protein (determined by immunoblotting) and PGI2 biosynthesis were diminished in HNSCC. In vitro experiments showed that the conditioning medium of HNSCC cell line (FaDu) modulated COX-2 expression in EC but not that of PGI-synthase. On the other hand, statistical correlation studies showed that PGI-synthase mRNA levels correlated with those of von Willebrand factor which were also lower in HNSCC.
Conclusions: These findings show that although COX-2 was over-expressed, HNSCC produced less PGI2 than paired non-tumoral mucosa. This was associated with a reduction of PGI-synthase expression that was probably caused by a decrease in the EC proportion in HNSCC, rather than to down-regulation of PGI-synthase in the strict sense. These findings suggest that modifier agents of PGI-synthase expression, such as retinoids, could have therapeutic value for HNSCC treatment. Our results indicates that PGIS expresión was asociated with radiotherapy efficiency, our results suggest that the effect of PGI2 is related to its ability to promote vascularization.